We are studying the mechanisms by which PCB's produce toxicity in fetal tissues with the goal of constructing a more rational basis for predicting drug and chemical toxicity to the fetus than is presently available. We are developing a model for evaluating the pathologic changes produced by PCB's in chick embryo liver. Using the chick embryo model we will investigate the dose-response and temporal relationships between the production of hepatotoxicity by different structural isomers of PCB's, their covalent binding to liver macromolecules and their induction of mixed function oxidase activity in embryos during development. We will examine the effects of experimental modification of mixed function oxidase activity and covalent binding on hepatotoxicity. We will further examine the relationship between the covalent binding of PCB's and the mixed function oxidase activity of human fetal tissues during the gestational period 10-20 weeks and the effects of maternal cigarette smoking on PCB binding to human fetal tissues and tissue mixed function oxidase activity.